- Development of long acting antiretroviral drugs tracking through molecular imaging technologies
- Development of on viral delivery and molecular imaging tracking system of CRISPR technology
- Monocyte-derived macrophages (MDMs) as drug delivery system-cell based vehicles for nanoparticle
- Development of virus like nanoparticles for targeting antiretroviral therapy and monitoring by nuclear medicine and molecular imaging technology
- Nano-cocrystal strategy for multi-drug antiretroviral therapy
- Synthesis of radiolabeled nanoparticles for nuclear medicine and molecular imaging technology for diagnostics as well as a therapeutic purpose
R01 MH121402-01A1 2019/12/01-2024/11/01
National Institute of Mental Health
The new field allows simultaneous detection (diagnostics) and treatment (therapeutic) for the identification and ultimate elimination of viral tissue compartments and cellular reservoir sites with a focus on the central nervous system. By employing theranostics viral entry sites in lymph nodes, gut and brain can be tracked during antiretroviral therapy (ART). Cellular viral targets including CD4+T cell populations and mononuclear phagocytes (MP; monocytes, macrophages, microglia and dendritic cells) subcellular endosomal structures can now be targeted for drug delivery in sites of active viral growth. The advantage of theranostics rests in that any steps towards improved HIV therapeutics and elimination strategies that requires precise targeted delivery of antiviral drugs. The long-term goal is to improve current therapeutic regimens with an emphasis on those that target the nervous system. This proposal seeks funds to accomplish this through improved HIV-1 drug monitoring, design of long acting, and gene editing technology to HIV-1 cure.
Role: MPI with Dash, P. and Gendelman, H.E.
P01 DA028555-06A1 PI: Gendelman, Howard E. 2009/12/01-2020/06/30
National Institute on Drug Abuse (NIDA)
NanoART Manufacture, Delivery and Pharmacokinetics for Optimizing Drug Adherence
This is an integrative cross approach translational and multi-investigator program grant seeking to develop nanoformulated antiretroviral drug therapy from the bench to the patient.
Potential Overlap: This P01 proposal provides an infrastructure for producing nanomedicines. The medicines being developed in the two grants are distinct, the modifications not related and the encasements requiring very different approaches.
COVID-19 Rapid Response Grants PI: St Patrick Reid 6/1/20 – 5/31/21
UNMC Nebraska Neuroscience Alliance
SARS-CoV-2-Macrophage Interactions for COVID-19 Neuropathobiology
The study of COVID-19 neuropathobiology allows us to characterize the human monocyte-macrophage-virus interactions linked to cell differentiation, activation, communication and bioactive factor secretion. We will decipher specific viral receptor regulations, cell signaling, epigenetic factor networks, inflammasome and each and all of their influences on contiguous neural vitality during the course of SARS-Cov-2 infection as a model system for CNS viral disease.
- Synthesis and characterizations: fluorescent doped multidrug co-nanocrystals production by anti-solvent precipitation, stability, and bioimaging applications | lanthanide-doped upconversion | cobalt ferrite | iron oxide | quantum dots nanoparticles | inorganic-organic nanocomposites | biomaterials for multimodal biomedical imaging | theranostic and drug delivery applications
- Pre-formulation/ formulation: formulations and physicochemical characterization studies of parenteral formulation | solid oral dosage | polymeric nanoformulations | layer by layer and fast dissolving oral strip films | content uniformity test | sterilization | pH solubility | adsorption isotherm | optimizations parameters and stability studies | lyophilization | disintegration | dissolution and stability testing | wet-milling | homogenization and single-emulsion techniques for nanoformulation manufacture process | scaling up of poorly water-soluble drug nanoparticles
- Advanced bioanalytical techniques: dissolutions | USP-II & IV (Sotax Automated system, USA) | Franz type diffusion cells (Perme Gear, Inc, USA) | SDI (Surface Dissolution Imager, Sirius, UK) | FTIR-ATR (Perkin–Elmer) |tangential flow filtration systems (TFF, Spectrum, Inc.) | Thermal Analyzer: DSC | TGA-DTA (Mettler Toledo and Perkin–Elmer) | UPLC (Waters, USA) | UV/Vis Spectrophotometer (Thermo Scientific, Shimadzu, Varian)
- Advanced particle engineering-techniques: powder X-ray diffraction (Rigaku, Japan) | particle size analysis & zetasizer (Malvern, Beckman, Rodos) | spray drier (Labultima) | FEM (Fluid Energy Milling) | high-pressure homogenizer (Avestin Inc, USA) | wet stirred media milling (Netzsch), etc.
- Electron and confocal microscopy techniques: scanning electron microscopy instrument handling (SEM, LEO-1530VP, UK) | transmission electron microscopy (TEM, FEI Tecnai Osiris, USA)
- Bioimaging technology: Single Photon Emission Computed Tomography (SPECT/CT) (TriFoil Imaging) | IVIS Spectrum In vivo Imaging System (Perkin Elmer, USA) | Confocal microscopy (LSM 810, Carl Zeiss Microimaging, Inc)
- In vitro drug actions/ toxicity in animal cell cultures: primary cell culture | macrophage isolation/raw macrophage characterizations |colocalization of nanoparticles in cells by primary and secondary antibodies labeling | viability assay | permeability assay | drug uptake | retention assay |antiretroviral activity, etc.
- Pharmacokinetic techniques: In vitro drug permeability | drug uptake kinetics and efficacy studies | In vivo pharmacokinetic | pharmacodynamic (PK/PD) and biodistribution studies involving tissue isolation | processing and drug estimations | histopathology and evaluation of biomarkers from plasma/ tissues
- In vitro drug release models: release kinetics | mathematical and computational modeling of drug adsorption in nanomatrix
- Software: Vivo-Quant-3.5 for PET/SPECT/CT image | post-processing | data analysis | Empower chromatography software | Origin 8.0 | Sigmaplot | Graphpad Prism® | Chem-draw 3D ultra | Minitab 16 | Adobe CS6 Illustrator | Adobe Photoshop |Blender | Flow Jo | EndNote® | ImageJ | Design of Experiment (DoE)